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Transport if loaded uclear transporters can be viewed as taxis that move cargo across the nuclear envelope. On page 649, Plafker et al. report that importin-11, a nuclear transport receptor , may be an especially selective cabbie. Importin-11 transports UbcM2, a ubiquitin (Ub)-conjugating enzyme, but it does so only when the enzyme is charged with a Ub at its active site. UbcM2 is an E2 enzyme, which works with E1 and E3 proteins to polyubiquitinate and tag proteins for degradation in the proteasome. To test whether importin-11 preferentially transports the Ub-charged UbcM2 or the unloaded enzyme, Plafker et al. performed coimmunoprecipitation assays with wild-type UbcM2, a mutant enzyme that is constitutively loaded with Ub, or a mutant that cannot be loaded. Importin-11 selectively bound the Ub-charged forms of UbcM2. Furthermore , in vitro pull-down assays showed that, if ATP or the E1 enzyme that loads Ub onto the UbcM2 active site were depleted, importin-11 did not bind UbcM2. In cell assays, catalytically inactive UbcM2 failed to localize to the nucleus. Only a subset of E2 enzymes bound to importin-11. This specific interaction may control the enzyme's access to potential substrates, including some involved in cell cycle progression. Plus, if importin-11 gobbles up all the Ub-charged UbcM2, then the enzyme cannot ubiquitinate cytoplasmic proteins. N ES cells without teratomas herapeutic use of embryonic stem cells may be hampered by their proclivity to form pluripotent tumors called teratomas. On page 723, Bieberich et al. describe the use of a ceramide analogue, S18, to induce apoptosis in a subpopulation of embryoid body–derived stem cells (EBCs). Cells that survive the treatment express the neural marker nestin and differentiate into neural progenitors when injected into the brains of young mice. They do not form teratomas. The S18 selectively affects those EBCs that express prostate apoptosis response-4 (PAR-4) protein, an endogenous inhibitor of atypical PKC ␨. Significantly, the majority of the PAR-4–expressing cells also express Oct-4, a marker for pluripotency. Almost all Oct-4 ϩ cells were positive for PAR-4, suggesting that teratoma formation might be prevented via elimination of PAR-4-expressing cells with ceramide-induced apoptosis before injection into animals. Sure enough, after injection into the brains of mice, treated cells differentiated into neural cells and some benign tumors, T but no invasive tumors. Untreated cells gave rise to a significant number of terato-mas in the same animals. Bieberich et al. hypothesize that coexpression of Oct-4 and PAR-4 …

T he risks and benefits of alcohol use vary across the life span. Even a small amount of alcohol may place a young driver at great risk behind the wheel. The same amount, howev er, could have health benefits for a middleaged man by reducing his risk of coronary heart disease. Dr. Mary C. Dufour introduces the concept of a "net outcome" of alcohol consump tion, which weighs both the potential positive and negative consequences of a person's drinking pattern to ar rive at a net benefit or risk for that person. Several examples show how this concept can be used to evaluate alcoholassociated outcomes across the life span and how these assess ments can translate into behavioral recommendations for people based on their specific drinking patterns and risk factors. (pp. 145-151)

THE NATURAL HISTORY OF ALCOHOLISM
A lcoholism is a chronic disease that may strike at any age. Some people develop the symptoms of al coholism after only months of heavy drinking, whereas other, "late onset," a lc oh o l i cs m a y d r i n k h e avil y f or years before developing the disease. To track the course of this complex disease over the life span, studies must monitor the same subjects over long periods of time. Dr. George E. V a i l l a n t a n d A l c o h o l H e a l t h & Research World Science Editor Dr. Susanne HillerSturmhöfel summa rize the findings of two such studies that have followed the evolution of alcoholism in several hundred men for the past 55 years. This research has led to important findings, includ ing the fact that alcoholism may or may not be progressive in nature. (pp. 152-161)

ALCOHOL'S ROLE IN WORKFORCE ENTRY AND RETIREMENT
E mployment and drinking behavior likely interact in a number of com plex ways. Dr. Paul M. Roman and J. Aaron Johnson explore these links in the context of two important life course junctures: workforce entry and retirement. The authors review findings that teenagers who work are actually more likely to drink than their unemployed peers and describe how early heavy drinking can chan nel young people into lowpaying, deadend jobs. For older adults, the association between work and alco hol use is less conclusive. The au thors discuss factors that may result in increased or decreased alcohol consumption during retirement and note that older adults who continue worki ng are m ore l ik el y to dri n k heavily than retirees. (pp. 162-169)

EFFECTS OF PRENATAL EXPOSURE TO ALCOHOL ACROSS THE LIFE SPAN
D rinking alcohol during pregnancy can adversely affect the develop ment of the fetus, resulting in lifelong medical consequences. Only recently have researchers begun to evaluate how prenatal alcohol exposure can af fect a child's school and, later, work performance. Drs. Paul D. Connor and Ann P. Streissguth discuss the changes occurring in the brain that lead to impaired attention, intelli gence, memory, motor coordination, complex problemsolving, and ab s t r a c t t h i n k i n g . T h e s e c o g n i t i v e deficits create longstanding emotion al and physiological problems. The authors conclude by discussing pre vention and treatment strategies to counter the effects of prenatal alcohol exposure. (pp. 170-174) DRINKING DURING ADOLESCENCE E xperimenting with alcohol use is common during adolescence and can spawn serious problems for some youth. These problems include ad verse medical consequences, health risks associated with unsafe sexual b e h a v i o r , u n i n t e n t i o n a l i n j u r i e s , homicide, and suicide. Dr. Laurie Chassin and Christian DeLucia re view the risk factors for adolescent alcohol use, categorizing them as so ciocultural, family related, peer re lated, or intrapersonal. The authors note that adolescents' beliefs about the effects of alcohol also influence drink ing behavior. These beliefs may be shaped by information accumulated from a range of sources, including the mass media. The specific risk factors that can predict problem drink ing among adolescents are not yet known, however. (pp. 175-180) EFFECT OF PARENTAL DRINKING ON ADOLESCENTS M any biological, psychological, and social changes occur during adolescence, and parents continue to play an important role in their chil dren's development during this peri od. Dr. Michael Windle describes how alcohol abuse can interfere with parenting skills and marital relations, thereby affecting adolescent develop ment and adjustment. Parents who abuse alcohol place their children at increased risk for alcohol and other drug use as well as for psychological problems. The author also reviews family (and nonfamily) factors that may offset the negative effects of parental drinking. (pp. 181-184) DRINKING AMONG YOUNG ADULTS Y oung adults ranging in age from the midteens to the late twenties have a higher prevalence of alcohol consumption and binge drinking than any other age group. They also drink more heavily than other age groups and experience more negative conse quences, such as traffic crashes. Drs. Lori A. Quigley and G. Alan Marlatt review studies on the prevalence, pat

IN THIS ISSUE
terns, and consequences of youthful drinking. Patterns of binge drinking change over time, and most heavy drinking youth appear to gradually reduce consumption (i.e., they "ma ture out" of abusive drinking). Accord ing to the authors, programs designed to reduce both the risks and conse quences of youthful drinking may help accelerate this maturingout process. (pp. 185-191)